A hybrid membrane-miomimetic nanoplatform for synergistic photothermal/photodynamic therapy of hypoxic tumors.

Breast cancer continues to be the primary malignancy impacting women globally. Traditional therapies are frequently limited by non-specific distribution of drugs, systemic toxic effects, and resistance to multiple drugs. Biomimetic nanotechnology offers a promising solution to overcome these barriers by enhancing tumor accumulation and therapeutic efficiency. Herein, we develop a biomimetic nanoparticle delivery system with bovine serum albumin (BSA) serving as a carrier molecule to co-load the photosensitizer indocyanine green (ICG) and the oxygen-carrying material perfluorohexane (PFH). The nanoparticles are camouflaged with a hybrid membrane obtained from 4T1 tumor cells and erythrocytes. The results demonstrated that this hybrid coating conferred these nanoparticles with prolonged circulation and homologous targeting capabilities, dramatically boosting accumulation at tumor sites. Moreover, PFH efficiently mitigates the hypoxic microenvironment of malignant tumors. Under 808 nm laser illumination, the synergistic photothermal and enhanced photodynamic therapy mediated by nanoparticles effectively ablated tumor tissues and exerted robust antitumor efficacy, prolonging the survival time of tumor-bearing mice. This study thus provides a hybrid membrane-based biomimetic nanoplatform for efficient therapy against hypoxic tumors.